Nonpolymeric Hydrogelator Derived from N-(4-Pyridyl)isonicotinamide

A series of pyridyl amides derived from isonicotinic acid, nicotinic acid, and benzoic ... Only N-(4-pyridyl)isonicotinamide 1 is found to be an effic...
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Langmuir 2004, 20, 10413-10418

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Nonpolymeric Hydrogelator Derived from N-(4-Pyridyl)isonicotinamide D. Krishna Kumar, D. Amilan Jose, Parthasarathi Dastidar,* and Amitava Das* Analytical Science Discipline, Central Salt & Marine Chemicals Research Institute, G. B. Marg, Bhavnagar - 364 002, Gujarat, India Received April 9, 2004. In Final Form: July 14, 2004 A series of pyridyl amides derived from isonicotinic acid, nicotinic acid, and benzoic acid have been synthesized. Only N-(4-pyridyl)isonicotinamide 1 is found to be an efficient hydrogelator with a minimum gelator concentration of 0.37 wt %. A wide range of concentrations (0.37-20 wt %) could be used to form hydrogels. The other amides, namely, N-(3-pyridyl)isonicotinamide 2, N-(2-pyridyl)isonicotinamide 3, N-(phenyl)isonicotinamide 4, N-(4-pyridyl)nicotinamide 5, N-(3-pyridyl)nicotinamide 6, and N-(4-pyridyl)benzamide 7, did not show any gelation properties. Fourier transform infrared spectroscopy, variable temperature 1H NMR, single-crystal diffraction and X-ray powder diffraction (XRPD), and scanning electron microscopy have been used to characterize the gel. Single-crystal diffraction and XRPD studies indicate that the morph responsible for gel formation is different from that in its bulk solid and xerogel.

Introduction Hydrogels are an important class of materials that display many interesting applications1 such as transport medium for dissolved species as a link between body fluids and synthetic implants, in drug delivery, in gel electrophoresis, in chemical sensing, as a biointerface, and as actuators. Classically, hydrogels are made from high molecular weight natural polymers such as gelatin,2 fibrin,3 and polysaccharide-derived polymers4 and also from synthetic molecules such as polymers of acrylic acid, ethylene oxide, vinyl alcohol, and other derivatives.5 Protein polymers6 are also known to form hydrogels, some of which are environmentally responsive to pH and temperature.7 However, the preparation of polymer-based hydrogels often suffers from constraints imposed by their thermosetting nature and lack of benefits associated with thermoplastic processing.8 Moreover, many hydrogels of this class are mechanically weak and do not have adequate water retention capacity, which limits their usefulness. * To whom correspondence should be addressed. Fax: +91-2782567562.E-mail: [email protected](P.D.);[email protected] (A.D.). (1) (a) Nishikawa, T.; Akiyoshi, K.; Sunamoto, J. J. Am. Chem. Soc. 1996, 118, 6110. (b) Osada, Y.; Gong, J. P. Adv. Mater. 1998, 10, 827. (c) Novick, S. J.; Dordick, J. S. Chem. Mater. 1998, 10, 955. (d) Ilmain, F.; Tanaka, T.; Kokufuta, E. Nature 1991, 349, 400. (e) Holtz, J. H.; Asher, S. A. Nature 1997, 389, 829. (f) Weissman, J. M.; Sunkara, H. B.; Tse, A. S.; Asher, S. A. Science 1996, 274, 959. (g) Osada, Y., Khokhlov, A. R., Eds. Polymer Gels and Networks; Marcel Dekker: New York, 2002. (h) Chu, Y. H.; Chen, J. K.; Whitesides, G. M. Anal. Chem. 1993, 65, 1314. (i) Lee, K.; Asher, S. A. J. Am. Chem. Soc. 2000, 122, 9534. (2) Kavanagh, G. M.; Ross-Murphy, S. B. Prog. Polym. Sci. 1998, 23, 533. (3) Perka, C.; Spitzer, R. S.; Lindenhayn, K.; Sittinger, M.; Schultz, O. J. Biomed. Mater. Res. 2000, 49, 305. (4) Chenite, A.; Chaput, C.; Wang, D.; Combes, C.; Buschmann, M. D.; Hoemann, C. D.; Leroux, J. C.; Atkinson, B. L.; Binette, F.; Selmani, A. Biomaterials 2000, 21, 2155. (5) Peppas, N. A.; Bures, P.; Leobandung, W.; Ichikawa, H. Eur. J. Pharm. Biopharm. 2000, 50, 27. (6) (a) Nowak, A. P.; Breedveld, V.; Pakstis, L.; Ozbas, B.; Pine, D. J.; Pochan, D.; Deming, T. J. Nature 2002, 417, 424. (b) Petka, W. A.; Harden, J. L.; McGrath, K. P.; Wirtz, D.; Tirrell, D. A. Science 1998, 281, 389. (c) Qu, Y.; Payne, S. C.; Apkarian, R. P.; Conticello, V. P. J. Am. Chem. Soc. 2000, 122, 5014. (7) (a) Lee, J.; Macosko, C. W.; Urry, D. W. Macromolecules 2001, 34, 4114. (b) McMillan, R. A.; Conticello, V. P. Macromolecules 2000, 33, 4809. (8) Shah, K. R. In Polymeric Materials Encyclopedia; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996; p 3092.

On the other hand, nonpolymeric self-assembly driven hydrogels derived from small molecules have attracted attention because of the amenability to tuning the gel properties by changing the chemical functionality, preparation conditions such as the pH and temperature, and composition of the aqueous solution. However, in contrast to their low molecular mass organic gelators (LMOGs),9 the examples of nonpolymeric hydrogels are indeed limited.10 This is due to the fact that LMOGs are often insoluble or poorly soluble in water as well as they display high crystallinity in water. Moreover, structural requirement for a molecule to be a hydrogelator is quite critical. It is believed that the careful balance between hydrophobic interactions and hydrogen bonding in water is required to achieve the essential three-dimensional elastic networks of these small gelator molecules within which the water molecules get immobilized. To achieve such a balance, it is important to have a hydrophobic moiety and multiple hydrogen bonding sites in the potential gelator molecules. Moreover, solubility in water is also an important point to be considered. We noticed in the Cambridge Crystallographic Database11 that mainly two types of hydrogen bonding patterns are present in pyridyl amides. Both are hydrogen bonded one-dimensional polymeric networks, which is believed to be one of the prerequisites for a molecule to become a potential gelator:9e one through a typical N-H‚‚‚O synthon involving the amide moiety and the other through a N-H‚‚‚N synthon involving the amide and pyridine ring nitrogen. If the amide functionality is flanked by two pyridine moieties, in either case, the network may be (9) (a) Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133. (b) Abdallah, D. J.; Weiss, R. G. Adv. Mater. 2000, 12, 1237. (c) Prost, J.; Rondelez, F. Nature 1991, 350, 11. (d) Grownwald, O.; Shinkai, S. Curr. Opin. Colloid Interface Sci. 2002, 7, 148. (e) van Esch, J.; Feringa, B. L. Angew. Chem. 2000, 112, 2351; Angew. Chem., Int. Ed. 2000, 39, 2263. (f) Grownwald, O.; Shinkai, S. Chem.sEur. J. 2000, 7, 4328. (g) Tiller, J. C. Angew. Chem., Int. Ed. 2003, 42, 3072. (h) Menger, F. M.; Peresypkin, A. V. J. Am. Chem. Soc. 2003, 125, 5340. (i) Menger, F. M.; Yamasaki, Y.; Catlin, K. K.; Nishimi, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 585. (j) Ko¨lbel, M.; Menger, F. M. Chem. Commun. 2001, 275. (k) Heeres, A.; van der Pol, C.; Stuart, M.; Friggeri, A.; Feringa, B. L.; van Esch, J. J. Am. Chem. Soc. 2003, 125, 14252. (10) Estroff, L. A.; Hamilton, A. D. Chem. Rev. 2004, 104, 1201 and references therein. (11) Allen, F. H.; Kennard, O. Chem. Des. Automat. News 1993, 8, 3137 (CSD version 5.24, Nov 2002).

10.1021/la049097j CCC: $27.50 © 2004 American Chemical Society Published on Web 10/23/2004

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Chart 1

Figure 1. Plot of Tgel (gel-sol dissociation temperature in °C) versus gelator concentration (wt %, w/v) of 1. Chart 2

Figure 2. DSC curves of the aqueous gel of 1 (10 wt %). Heating and cooling rate: 5 °C/min.

envisaged as one-dimensional wherein pyridine ring nitrogen atoms are also available for further hydrogen bonding (Chart 1). Because hydrophobicity (due to the heterocyclic aromatic ring), the plausible one-dimensional hydrogen bonded network (either motif A or B, Chart 1), and the expected solubility in water due to pyridine moieties are present in this class of molecules, we have synthesized a series of pyridyl amides as possible hydrogelators (Chart 2). Out of seven amides (1-7), only N-(4-pyridyl)isonicotinamide 1 is found to be an efficient hydrogelator, and this paper describes its gelation behavior and structure. Results and Discussion All the amides 1-7 are sparingly soluble in water at room temperature. However, upon heating at ∼90 °C, all of them become soluble in water. On cooling to 25 °C, only 1 gives a translucent gel (which does not show any physical deformity upon inversion of the test tube), and the others do not produce a gel. The amide 1 turns out to be a highly efficient gelator of water. The minimum gelator concentration (MGC) of 1 is found to be 0.37 wt %, meaning that one molecule of the gelator is able to rigidify ∼3030 molecules of water. To estimate the thermal stability of the gel, a plot of the gel-sol dissociation temperature (Tgel)22 versus gelator concentration is examined. Figure 1 clearly indicates that, with the increase in gelator concentration, Tgel increases, which means that the aggregation of the gelator molecules during gelation is driven by strong supramolecular interactions. It is interesting to note that the gelator is highly soluble in water upon heating, and it is possible to form a thermoreversible gel even at 20 wt % (Tgel ) 79 °C). The gelation behavior of 1 is quite pH sensitive. The pH of the aqueous solution of 1 is found to be 7.7 at the MGC. When the pH is changed to 5.0 using 1% AcOH (v/v), it fails to form gel. On the other hand, when gelation experiments are performed at pH 8-11 using NaHCO3, a gel is formed. These results clearly indicate that the free pyridine nitrogen atoms might be contributing toward

Figure 3. SEM of the xerogel of 1: (a) 0.37 wt % (bar ) 20 µm); (b) 20 wt % (bar ) 10 µm).

the required self-assembly of the gelator molecules through possible hydrogen bonding. To provide further support to this hypothesis, a monohydrochloride salt 8 of the gelator 1 has been synthesized (Chart 2), and it also turns out to be a nongelator. This indicates that both the ring nitrogen atoms of the gelator 1 must be free from protonation to form a gel. A 10.0 wt % gel of 1 shows an endothermic phase transition from gel to sol at 81 °C whereas in the corresponding cooling cycle, the exothermic phase transition from sol to gel appears at 44 °C in a differential scanning calorimetry (DSC) experiment (Figure 2). Observation under a low resolution optical microscope equipped with a cross polar reveals that the typical fibrous nature of the gel (0.5 wt %) and the fibers, often radiating from central points, is optically birefringent displaying its crystalline nature. To see the morphology of the fibers in more detail, scanning electron microscopy (SEM) pictures at the MGC are recorded. Figure 3a depicts the SEM picture of the xerogel of 1 at the MGC. The morphology of the fibers appears to have tape architecture. The widths of the tapes range from 0.57 to 5.7 µm. Because 1 is able to form a thermo-reversible gel even at a very high concentration such as 20 wt %, SEM is also recorded to see the morphology of the fibers at this concentration. Figure 3b displays the SEM of the xerogel of 1 at 20 wt %. In this

Nonpolymeric Hydrogelator

Figure 4. 1H NMR spectra of the aqueous gel of 1 in D2O at various temperatures.

case, the morphology of the fibers is also found to be of tape type and the widths range from 1.65 to 5.5 µm. Fibers in both the cases form a complicated three-dimensional network. Understandably, the solvent water molecules are immobilized in such a three-dimensional network of fibers, resulting into gel formation. Fourier transform infrared (FT-IR) spectroscopy of the bulk solid, xerogel, and crystals (grown from EtOH) of 1 appears to be virtually identical, meaning that the internal structure of the gelator molecule in the bulk solid is identical to its xerogel as well as crystals grown from EtOH. The amide I band in these cases appears at 1688 cm-1. Interestingly, the amide I band in the gel state (D2O) appears at 1672 cm-1. The 16 cm-1 shift of the CdO stretching may be attributed to further hydrogen bonding either involving CdO and solvent water molecules or rearranged self-assembly of the gelator molecules. To provide further insights into the self-assembly process during gelation, 1H NMR (D2O) experiments have been performed on an aqueous 0.9 wt % gel of 1 at various temperatures. Thus, at 25 °C, the Ha and Hd protons appear at δ 8.77 and 8.53 respectively, whereas Hb and Hc appear at 7.87-7.82. At 65 °C the corresponding signals are obtained at δ 9.45 (Ha), 9.22 (Hb), and 8.53-8.39 (Hb and Hc). Therefore, all the aromatic protons have been gradually shifted downfield while heating the sample from 25 to 65 °C (Figure 4). This observation may be attributed to the ordered self-assembly of the gelator molecule in the gel state probably through π-π stacking interactions.12 Although both hydrogen bonding and hydrophobic interactions play an important role in the gelation process of the hydrogel, it is considered worthwhile to study the hydrogen bonding interactions in these compounds in their crystalline state to address the important structural issue: what, if any, is the relationship between the molecular packing of the bulk crystals of a compound and its gelation behavior.9a Fortunately, X-ray quality crystals of all the amides except 6 can be grown. The structure of 4-pyridyl benzamide 7 is already available in the literature.13 The single-crystal structure of the monohydrochloride salt 8 of the gelator 1 is also investigated to compare the corresponding supramolecular assemblies of the protonated 8 and nonprotonated form 1. Figure 5 depicts the supramolecular assemblies of the corresponding molecules (1-5 and 8) in their crystal structures. While 1, 4, and 5 display a one-dimensional hydrogen bonded (12) Jung, J. H.; Shinkai, S.; Shimizu, T. Chem.sEur. J. 2002, 8, 2684. (13) Noveron, J. C.; Lah, M. S.; Del Sesto, R. E.; Arif, A. M.; Miller, J. S.; Stang, P. J. J. Am. Chem. Soc. 2002, 124, 6613.

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network through the N-H‚‚‚N (in 1), N-H‚‚‚O (in 4), and both N-H‚‚‚N and N-H‚‚‚O (in 5) hydrogen bonds, participation of water molecules in the crystal lattice of 2 makes the network three-dimensional. On the other hand, the molecules in the crystal structure of 4 are assembled mainly through dispersion force into a twodimensional sheet structure wherein the individual molecules appear to be assembled via very weak NH‚‚‚N hydrogen bonding. The crystal structure of 713 also displays a one-dimensional hydrogen bonded polymeric network through N-H‚‚‚N interactions involving amide and pyridine ring nitrogen atoms. It is believed, on the basis of single-crystal structures of some organogelators,14,15 that the one-dimensional hydrogen bonded network may induce the one-dimensional growth of the gel fibril, whereas the growth perpendicular to the fibril axis is slower because of interaction with the solvent molecules, and, therefore, molecules that tend to form one-dimensional hydrogen bonded network have a better chance of showing gelation properties. Although the gelation ability of 1 and nongelling behavior of 2 and 3 can be easily correlated with their corresponding crystal structures (one-dimensional network for 1, three-dimensional network for 2, and two-dimensional network for 3), the nongelling behavior of 4, 5, and 7 cannot be correlated with the hydrogen bonding network (all one-dimensional) observed in their corresponding crystal structures. Thus, the present findings from the crystals structures of the compounds studied here indicate that the supramolecular process of aggregating the gelator molecules to form a gel fibril is much more complicated than the simplistic view stated above. However, it may be noted here that the main differences in the molecular structures of these amides arise due to the fact that, in gelator 1, the ring nitrogen atoms are linearly oriented, whereas in others (2, 3, and 5) the relative positions of the ring nitrogen atoms are not linear and there is only one ring nitrogen atom present in 4 and 7. Therefore, the relative orientation and the number of ring nitrogen atoms seem to be important for gel fibril formation. Because the monoprotonated form 8 of the gelator is a nongelator, it is considered worthwhile to investigate its single-crystal structure. In 8, the monoprotonated molecules are self-assembled through N-H‚‚‚N hydrogen bonding involving protonated ring nitrogen atoms with the nonprotonated counterpart to form a one-dimensional hydrogen bonded network. Counterion Cl- and water of crystallization are found to form a bridge between two such one-dimensional hydrogen bonded chains of the monoprotonated amides resulting in an overall onedimensional tape type of network (Figure 5f). Therefore, none of the pyridine ring nitrogen atoms are available for further hydrogen bonding in 8, which is in contrast to its parent unprotonated structure (in 1) wherein one of the pyridine ring nitrogen is available for further hydrogen bonding. The crystalline morph of the gel fibril needs not necessarily be the same as that in the corresponding xerogel because morphological transformation might take place during solvent removal for xerogel preparation or it might be initiated by some nucleation events induced by the small amount of soluble gelator molecules present in the bulk liquid in the gel state. To probe whether such (14) (a) Luboradzki, R.; Gronwald, O.; Ikeda, M.; Shinkai, S.; Reinhoudt, D. N. Tetrahedron 2000, 56, 9595. (b) Tamaru, S.-I.; Luboradzki, R.; Shinkai, S. Chem. Lett. 2001, 336. (15) (a) Ballabh, A.; Trivedi, D. R.; Dastidar, P. Chem. Mater. 2003, 15, 2136. (b) Trivedi, D. R.; Ballabh, A.; Dastidar, P. Chem. Mater. 2003, 15, 3971.

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Figure 5. Association modes of the molecules through hydrogen bonds and other nonbonded interactions as obtained in their corresponding single-crystal structures. (a) One-dimensional network through the N-H‚‚‚N hydrogen bond in 1; (b) water-mediated three-dimensional hydrogen bonding network in 2; (c) two-dimensional layer arising from the dispersion force and one-dimensional network through weak N-H‚‚‚N interactions in 3; (d) one-dimensional network through weak N-H‚‚‚O interactions in 4; (e) one-dimensional network arising from an unusual alternating N-H‚‚‚O and N-H‚‚‚N hydrogen bonding in 5; (f) one-dimensional tape architecture involving N-H‚‚‚N, N-H‚‚‚Cl-, and O-H‚‚‚Cl- interactions in 8. Scheme 1. Schematic Representation of the Molecular Association in the Xerogel Fibrils of 1 As Concluded from XRPD Experiments

Figure 6. XRPD patterns at various conditions of 1.

a transformation is indeed taking place, the simulated powder diffraction pattern obtained from single-crystal X-ray diffraction data and X-ray powder diffraction (XRPD) of the bulk solid, xerogel, and gel of 1 are compared (Figure 6). XRPD of the gel is recorded using a highly concentrated solution of 1 (20 wt %) because the patterns below 20 wt % are highly masked by the scattering of water. It is clear from Figure 6 that the simulated, bulk solid and xerogel XRPD patterns are virtually super-

imposable, meaning that the single-crystal structure of 1 truly represents the molecular packing in its bulk solid and gel fibers of the xerogel. Therefore, the aggregation mode of the molecules in xerogel fibrils is established (Scheme 1). However, the XRPD pattern of the gel is found to be different. Therefore, it appears that the morph responsible for hydrogel formation is quite different from that present in the xerogel or bulk solid. Because solubility and crystallinity may have a significant impact on gelation, solubility of all the compounds in water at 25 °C has been measured. Most of the

Nonpolymeric Hydrogelator

Langmuir, Vol. 20, No. 24, 2004 10417 Table 1. Crystallographic Parameters for 1-5 and 8

crystal data empirical formula FW crystal size (mm), color crystal system space group a, Å b, Å c, Å r/0 β/0 γ/0 volume, Å-3 Z Dcalc F(000) µ Mo KR (mm-1) temperature (K) observed reflections [I > 2σ(I)] parameters refined goodness of fit final R1 on observed data final wR2 on observed data

1

2

3

4

5

8

C11H9N3O

C11H11N3O2

C11H9N3O

C12H10N2O

C22H18N6O2

C22H22Cl2N6O3

199.21 0.31 × 0.21 × 0.17, colorless orthorhombic Pbcn 14.169(7) 8.920(6) 15.709(13) 90.00 90.00 90.00 1985(2) 8 1.333 832 0.090 293(2) 822

217.23 0.56 × 0.33 × 0.18, pale yellow orthorhombic Pbca 24.983(11) 12.394(5) 7.039(3) 90.00 90.00 90.00 2179.6(16) 8 1.324 912 0.094 293(2) 859

199.21 0.67 × 0.43 × 0.19, colorless monoclinic P21/n 8.3652(8) 13.5971(13) 8.7826(9) 90.00 102.248(2) 90.00 976.22(17) 4 1.355 416 0.092 293(2) 1722

198.22 0.55 × 0.34 × 0.11, pale yellow triclinic P1 h 5.3406(7) 7.8247(10) 12.1855(15) 74.337(2) 79.174(2) 89.913(2) 480.93(11) 2 1.369 208 0.090 293(2) 1877

398.42 0.34 × 0.26 × 0.23, colorless triclinic P1h 8.703(6) 10.393(4) 12.564(5) 95.37(3) 108.00(5) 112.87(6) 965.8(9) 2 1.370 416 0.093 293(2) 1877

489.35 0.74 × 0.59 × 0.29, colorless triclinic P1 h 8.6136(9) 11.5406(12) 11.9548(12) 80.317(2) 75.454(2) 85.618(2) 1133.2(2) 2 1.434 508 0.324 293(2) 3780

173

189

172

176

343

386

0.931 0.0412

1.149 0.0715

1.043 0.0536

1.086 0.0452

0.997 0.0420

1.063 0.0435

0.0956

0.1908

0.1333

0.1213

0.0988

0.1216

Table 2. Hydrogen Bonding Parameters of 1-5 and 8 D-H‚‚‚A 1 N(9)-H(9)‚‚‚N(1) 2 N(9)-H(9)‚‚‚O(16) O(16)-H(16A)‚‚‚N(1) O(16)-H(16B)‚‚‚N(14) 3 N(9)-H(9)‚‚‚N(1) 4 N(9)-H(9)‚‚‚O(8) 5 N(9′)-H(9′)‚‚‚O(8) N(9)-H(9)‚‚‚N(13′) 8 N(9)-H(9)‚‚‚Cl(1) N(13)-H(13)‚‚‚N(1) O(16)-H(17A)‚‚‚Cl(1) O(16)-H(17B)‚‚‚Cl(1′) N(9′)-H(9′)‚‚‚Cl(1′) N(13′)-H(13′)‚‚‚N(1′)

∠D-H‚‚‚A

D-H

H‚‚‚A

D‚‚‚A

symmetry operation for A

0.89(3)

2.06(3)

2.953(3)

174(3)

-x + 0.5, y - 0.5, z

0.91(3) 1.14(7) 0.77(5)

1.99(4) 1.76(7) 2.09(5)

2.885(4) 2.887(5) 2.819(4)

169(3) 171(5) 159(5)

-x, -y + 0.5, z + 0.5 -x + 0.5, y - 0.5, z -x, -y + 1, -z + 1

0.82(2

2.57(2)

3.3913(19)

172.1(17)

x + 0.5, -y + 0.5, z + 0.5

0.862(17)

2.337(17)

3.1522(15)

157.7(13)

x + 1, y, z

0.83(2) 0.85(2)

2.18(2) 2.11(2)

3.001(3) 2.956(4)

173(2) 169.6(19)

x, y, z x + 1, y + 1, z

0.84(2) 0.92(2) 0.90(3) 0.82(3) 0.84(2) 0.94(3)

2.47(2) 1.88(3) 2.31(3) 2.40(3) 2.43(2 1.85(3)

3.2926(16) 2.7893(19) 3.200(2) 3.213(2) 3.2640(16) 2.7752(19)

164.5(19) 168(2) 171(3) 174(3) 169.9(18) 167(2)

x, y, z x, y, z + 1 -x + 1, -y + 1, -z + 1 -x + 1, -y + 1, -z + 1 x + 1, y, z x, y, z - 1

nongelator amides 2, 3, 5, and 6 are found to be more soluble than the gelator 1, and monoprotonated amide 8 is found to be extremely soluble in water. On the other hand, 4 and 7 have solubility comparable to that of 1 (Supporting Information). Less solubility of 1 probably helps the molecules aggregate in required superstructures during gel formation. The fact that 4 and 7 are nongelator despite having solubility comparable to that of 1 may be because of the fact that in both the compounds, there is only one ring nitrogen atom in contrast to the gelator molecule 1.

free from protonation to form a gel. Gel formation is observed in a wide range of gelator concentrations (0.3620 wt %, w/v), which leaves room to play with the physical property of the gel. Variable-temperature 1H NMR experiments reveal that in the gel state the gelator molecules are quite ordered in nature probably through π-π stacking interactions. Both FT-IR and XRPD experiments indicate that the superstructure of the fibril in the gel state is different from that in its bulk solid or xerogel state.

Conclusions

Materials and Physical Measurements. All chemicals are commercially available (Aldrich) and used without further purification. Microanalyses are performed on a Perkin-Elmer elemental analyzer 2400, Series II. FT-IR and NMR spectra were recorded using Perkin-Elmer Spectrum GX and 200 MHz Bruker Avance DPX200 spectrometers, respectively. Powder X-ray patterns are recorded on an XPERT Philips (Cu KR radiation) diffractometer. SEM is performed on a LEO 1430VP. DSC analyses are performed on a Mettler Toledo DSC 822e. General Methods of Syntheses. All amides 2-7 are synthesized by the standard reaction between the corresponding

The present example, that is, N-(4-pyridyl)isonicotinamide 1, definitely represents an efficient hydrogelator with remarkably low molecular weight. Nongelling behavior of related amides (2-7) indicates that the number of ring nitrogen atoms and their relative position are important for gel formation. The fact that 1 does not form a gel either at pH 5.0 or in its monoprotonated form 8 clearly shows that both the ring nitrogen atoms must be

Experimental Section

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acid and amine in the presence of Et3N. 1 is synthesized by following the reported procedure.16 The monohydrochloride salt 8 of the gelator is prepared by excluding the bicarbonate-washing step from the synthetic procedure of the gelator. Analytical Data. 1: mp 196 °C. Anal. Calcd for C11H9N3O: C, 66.32; H, 4.55; N, 21.09. Found: C, 65.86; H, 4.85; N, 21.02. 1H NMR (MeOD): 8.75 (d, J ) 6 Hz, 2H), 8.49 (d, J ) 8 Hz, 2H), 7.92-7.83 (m, 4H). FT-IR (KBr, cm-1): 3303w, 3238w, 3154m, 3056w, 2998w, 2958m, 2881m, 2815m, 2741w, 2454w, 1960m, 1870w, 1811w, 1688vs, 1619m, 1592vs, 1556m, 1524vs, 1487s, 1413s, 1330s, 1305vs, 1261m, 1227w, 1207m, 1124m, 1094w, 1062s, 991m, 860s, 825s, 756s, 719m, 689m, 660w, 593s, 542s, 507s. 2: mp 162-164 °C. Anal. Calcd for C11H11N3O2 (molecular formula includes one molecule of H2O): C, 60.82; H, 5.10; N, 19.34. Found: C, 60.65; H, 4.80; N, 18.27. 1H NMR (MeOD): 8.912 (s, 1H), 8.767 (d, J ) 4.6 Hz, 3H), 8.352-8.258 (m, 3H), 7.927 (d, J ) 5 Hz, 3H), 7.501-7.438 (m, 1H). FT-IR (KBr, cm-1): 3310m, 3194w, 3130w, 3105w, 3069w, 3048w, 3015w, 2918w, 2855w, 2360w, 2284w, 1974m, 1923w, 1872w, 1849w, 1680vs, 1623s, 1589s, 1555vs, 1480s, 1427vs, 1329w, 1307vs, 1242w, 1220m, 1137m, 1103w, 1067w, 1052m, 1023m, 999s, 971w, 938m, 895m, 854m, 840m, 813s, 790w, 756s, 701vs, 666w, 629s, 594m, 522s, 491w, 421w, 406m. 3: mp 136-138 °C. Anal. Calcd for C11H9N3O: C, 66.32; H, 4.55; N, 21.09. Found: C, 65.62; H, 4.29; N, 20.36. 1H NMR (MeOD): 8.748 (s, 2H), 8.363 (s, 1H), 8.245 (d, J ) 8.2 Hz, 1H), 7.902-7.801 (m, 3H), 7.208-7.153 (m, 1H). FT-IR (KBr, cm-1): 3294w, 3199w, 3155w, 3047m, 3002w, 2900w, 1987w, 1957w, 1911w, 1870w, 1839w, 1732w, 1679vs, 1604w, 1592w, 1577s, 1557m, 1535vs, 1495s, 1460m, 1431vs, 1339m, 1308vs, 1262m, 1238m, 1227m, 1147s, 1121m, 1104w, 1088w, 1065s, 991s, 968w, 957w, 894m, 873m, 848m, 781vs, 749s, 690s, 622m, 597s, 520s, 468w, 421w, 406m. 4: mp 186-188 °C. Anal. Calcd for C12H10N2O: C, 72.71; H, 5.08; N, 14.13. Found: C, 72.80; H, 4.59; N, 22.32. 1H NMR (MeOD): δ 8.745 (d, J ) 5 Hz, 2H), 7.898 (d, J ) 4.6 Hz, 2H), 7.727 (d, J ) 8 Hz, 2H), 7.415-7.339 (m, 2H), 7.210-7.139 (m, 1H). FT-IR (KBr, cm-1): 3342vs, 3128w, 3076w, 3060w, 3044m, 2790w, 2649w, 1943w, 1770w, 1657vs, 1601s, 1532vs, 1492m, 1442vs, 1407s, 1325s, 1266s, 1215m, 1177m, 1157w, 1119w, 1066m, 1031m, 1002w, 986m, 961w, 909m, 889m, 847m, 820m, 750vs, 712m, 690s, 650s, 585m, 507s, 429w. 5: mp 186-188 °C. Anal. Calcd for C11H9N3O: C, 66.32; H, 4.55; N, 21.09. Found: C, 65.77; H, 4.78; N, 22.93. 1H NMR (MeOD): 9.10 (s, 1H), 8.76 (d, 1H), 8.47-8.36 (m, 3H),7.85 (d, J ) 4 Hz, 2H), 7.64-7.58 (m, 1H). FT-IR (KBr, cm-1): 3308m, 3276m, 3186m, 3154w, 3037w, 2981w, 2949w, 2887w, 2817w, 1951w, 1795w, 1734w, 1694s, 1658s, 1615w, 1592vs, 1533s, 1513vs, 1439w, 1419vs, 1339vs, 1315s, 1219s, 1215s, 1193m, 1132w, 1115m, 1096m, 1066w, 1024m, 997m, 968m, 940w, 894w, 850m, 829s, 741m, 711s, 663m, 622m, 584s, 536s, 500m, 407m. 6: mp 182-184 °C. Anal. Calcd for C11H9N3O: C, 66.32; H, 4.55; N, 21.09. Found: C, 65.22; H, 4.84; N, 22.13. 1H NMR (MeOD): 9.116 (s, 1H), 8.904 (s, 1H), 8.753 (d, J ) 4.6 Hz, 1H), 8.396-8.248 (m, 3H), 7.628-7.421 (m, 2H). FT-IR (KBr, cm-1): 3286w, 3243m, 3184m, 3122w, 3104w, 3068m, 3047w, 3005w, 2955w, 2895w, 2831w, 2661w, 1980w, 1956w, 1941w, 1771w, 1732w, 1679vs, 1609s, 1587vs, 1547vs, 1484s, 1472m, 1428s, (16) Gardner, T. S.; Wenis, E.; Lee, J. J. Org. Chem. 1954, 19, 753.

Kumar et al. 1331s, 1291vs, 1238m, 1190m, 1134m, 1114s, 1040m, 1022s, 969w, 929m, 886m, 842m, 816s, 712m, 701s, 628s, 597w, 521w, 470m, 416m. 8: mp >300 °C. Anal Calcd for C22H22Cl2N6O3: C, 52.08; H, 4.77; N, 16.56. Found: C, 52.82; H, 5.44; N, 15.22. 1H NMR (MeOD): 8.826-8.675 (m, 4H), 8.318 (d, J ) 7.2 Hz, 2H), 7.9757.946 (m, 2H). FT-IR (KBr, cm-1): 3688w, 3409m, 3202w, 3084m, 3040w, 3018m, 2924w, 2814m, 2504w, 2125w, 2029w, 1961w, 1697vs, 1639vs, 1588vs, 1509vs, 1421m, 1398w, 1326s, 1299s, 1274m, 1254w, 1226w, 1194s, 1117m, 1102w, 1068m, 1052m, 1010s, 978m, 891m, 875w, 847s, 830m, 756s, 716w, 695vs, 649w, 579m, 530s, 442w. Single-Crystal X-ray Diffraction. X-ray quality single crystal of 1 is obtained from MeOH, 5, and 8 from water at room temperature. Crystals of 2-4 are obtained from a water/MeOH mixture. Diffraction data for 3, 4, and 8 are collected using Mo KR (λ ) 0.7107 Å) radiation on a SMART APEX diffractometer equipped with charge-coupled device area detector. Data for other crystals 1, 2, and 5 are collected using Mo KR (λ ) 0.7107 Å) radiation on a CAD-4 diffractometer. Data collection, data reduction, and structure solution/refinement are carried out using the software package of SMART APEX for 3, 4, and 8 whereas the corresponding calculations are performed for the data collected on CAD-4 using CAD4-PC,17 NRCVAX,18 and SHELX97.19 Graphics are generated using PLATON20 and MERCURY 1.1.1.21 All structures are solved by direct methods and refined in a routine manner. In all cases, nonhydrogen atoms are treated anisotropically. Whenever possible, the hydrogen atoms are located on a difference Fourier map and refined. In other cases, the hydrogen atoms are geometrically fixed. The crystallographic parameters are listed in Table 1. The hydrogen bonding parameters are given in Table 2.

Acknowledgment. We thank all the reviewers for their valuable comments and suggestions. Department of Science and Technology and Ministry of Environment and Forests, New Delhi, is thankfully acknowledged for financial support. Dr. P. K. Ghosh is thanked for his support. Supporting Information Available: Solubility data of 1-8 and ORTEP diagrams of 1-5 and 8 (PDF). This material is available free of charge via the Internet at http://pubs.acs.org. LA049097J (17) CAD-4 Software, version 5.0; Enraf-Nonius: Delft, 1989. (18) Gabe, I.; Page, Y. L.; Charland, I. P.; Lee, F. L.; While, P. S. J. Appl. Crystallogr. 1989, 22, 384. (19) Sheldrick, G. M. SHELEXL-97, A program for crystal structure solution and refinement; University of Go¨ttingen: Go¨ttingen, Germany, 1993. (20) Spek, A. L. PLATON-97; University of Utrecht: Utrecht, The Netherlands, 1997. (21) Mercury 1.1.1 Supplied with Cambridge Structural Database; CCDC: Cambridge, U.K., 2001-2002. (22) Tgel was measured by the drop ball method. A custom-made glass ball weighing 0.19 g was placed on the gel surface, and the gel was heated gradually in an oil bath. The temperature at which the ball fell into the bottom of the test tube was recorded as the gel dissociation temperature (Tgel).